2YG2

Structure of apolioprotein M in complex with Sphingosine 1-Phosphate

2YG2 の概要

• エントリーDOI: 10.2210/pdb2yg2/pdb
• 関連するPDBエントリー: 2WEW 2WEX
• 分子名称: APOLIPOPROTEIN M, (2S,3R,4E)-2-amino-3-hydroxyoctadec-4-en-1-yl dihydrogen phosphate, CITRATE ANION, ... (4 entities in total)
• 機能のキーワード: lipid transport, lipocalin, hdl
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Secreted: O95445
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39433.62

構造登録者

Christoffersen, C.,Obinata, H.,Gowda, S.,Galvani, S.,Ahnstrom, J.,Sevvana, M.,Egerer-Sieber, C.,Muller, Y.A.,Hla, T.,Nielsen, L.,Dahlback, B. (登録日: 2011-04-11, 公開日: 2011-06-01, 最終更新日: 2023-12-20)

主引用文献

Christoffersen, C.,Obinata, H.,Kumaraswamy, S.B.,Galvani, S.,Ahnstrom, J.,Sevvana, M.,Egerer-Sieber, C.,Muller, Y.A.,Hla, T.,Nielsen, L.B.,Dahlback, B.
Endothelium-Protective Sphingosine-1-Phosphate Provided by Hdl-Associated Apolipoprotein M.
Proc.Natl.Acad.Sci.USA, 108:9613-, 2011

PubMed Abstract: Protection of the endothelium is provided by circulating sphingosine-1-phosphate (S1P), which maintains vascular integrity. We show that HDL-associated S1P is bound specifically to both human and murine apolipoprotein M (apoM). Thus, isolated human ApoM(+) HDL contained S1P, whereas ApoM(-) HDL did not. Moreover, HDL in Apom(-/-) mice contains no S1P, whereas HDL in transgenic mice overexpressing human apoM has an increased S1P content. The 1.7-Å structure of the S1P-human apoM complex reveals that S1P interacts specifically with an amphiphilic pocket in the lipocalin fold of apoM. Human ApoM(+) HDL induced S1P(1) receptor internalization, downstream MAPK and Akt activation, endothelial cell migration, and formation of endothelial adherens junctions, whereas apoM(-) HDL did not. Importantly, lack of S1P in the HDL fraction of Apom(-/-) mice decreased basal endothelial barrier function in lung tissue. Our results demonstrate that apoM, by delivering S1P to the S1P(1) receptor on endothelial cells, is a vasculoprotective constituent of HDL.

PubMed: 21606363
DOI: 10.1073/PNAS.1103187108

実験手法

X-RAY DIFFRACTION (1.7 Å)